Skip to main content
Log in

Performance of cystatin C-based equations in a pediatric cohort at high risk of kidney injury

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Limited data exist on the performance of cystatin C-based glomerular filtration rate (GFR) equations in pediatric transplant recipients and other high-risk patients. The aim of our study was therefore to evaluate the performance of current cystatin C-based equations in this population.

Methods

This was a retrospective, cross-sectional study of 141 consecutive patients (58 % post-transplant) who received a nuclear medicine GFR (NucGFR) examination using 99mTc- diethylenetriaminepentaacetic acid at our institution. Subjects included children receiving liver, kidney or hematopoietic stem cell transplants and patients with oncologic or urologic disease. GFR estimates using published GFR estimating equations, including those based on cystatin C (Filler, Zappitelli, Larsson, Hoek, Rule and Le Bricon equations, respectively) and on both cystatin C and creatinine (Zappitelli, Bouvet and Schwartz equations, respectively), were evaluated and compared to the NucGFR measurement using Bland–Altman analysis.

Results

The mean NucGFR was 95 (interquartile range 76–111)  ml/min/1.73 m2. Of the cystatin C-based equations, the Rule, Hoek, Zappitelli and Schwartz (2009 CKiD equation) formulas provided the closest agreement to the NucGFR estimate. All other formulas overestimated the GFR in our cohort.

Conclusion

Cystatin C-based GFR formulas can provide an accurate estimation of NucGFR in a pediatric population with a high proportion of transplant recipients and oncology patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Dharnidharka VR, Kwon C, Stevens G (2002) Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 40:221–226

    Article  PubMed  CAS  Google Scholar 

  2. Filler G, Bokenkamp A, Hofmann W, Le Bricon T, Martinez-Bru C, Grubb A (2005) Cystatin C as a marker of GFR—history, indications, and future research. Clin Biochem 38:1–8

    Article  PubMed  CAS  Google Scholar 

  3. Bokenkamp A, Domanetzki M, Zinck R, Schumann G, Byrd D, Brodehl J (1998) Cystatin C–a new marker of glomerular filtration rate in children independent of age and height. Pediatrics 101:875–881

    Article  PubMed  CAS  Google Scholar 

  4. Filler G, Witt I, Priem F, Ehrich JH, Jung K (1997) Are cystatin C and beta 2-microglobulin better markers than serum creatinine for prediction of a normal glomerular filtration rate in pediatric subjects? Clin Chem 43:1077–1078

    PubMed  CAS  Google Scholar 

  5. Bokenkamp A, Domanetzki M, Zinck R, Schumann G, Brodehl J (1998) Reference values for cystatin C serum concentrations in children. Pediatr Nephrol 12:125–129

    Article  PubMed  CAS  Google Scholar 

  6. Filler G, Lepage N (2003) Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula? Pediatr Nephrol 18:981–985

    Article  PubMed  Google Scholar 

  7. Grubb A, Nyman U, Bjork J, Lindstrom V, Rippe B, Sterner G, Christensson A (2005) Simple cystatin C-based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan–Barratt prediction equations for children. Clin Chem 51:1420–1431

    Article  PubMed  CAS  Google Scholar 

  8. Zappitelli M, Parvex P, Joseph L, Paradis G, Grey V, Lau S, Bell L (2006) Derivation and validation of cystatin C-based prediction equations for GFR in children. Am J Kidney Dis 48:221–230

    Article  PubMed  CAS  Google Scholar 

  9. Filler G, Priem F, Vollmer I, Gellermann J, Jung K (1999) Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate. Pediatr Nephrol 13:501–505

    Article  PubMed  CAS  Google Scholar 

  10. Martini S, Prevot A, Mosig D, Werner D, van Melle G, Guignard JP (2003) Glomerular filtration rate: measure creatinine and height rather than cystatin C! Acta Paediatr 92:1052–1057

    Article  PubMed  CAS  Google Scholar 

  11. Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637

    Article  PubMed  Google Scholar 

  12. Balachandran S, Toguri AG, Petrusick TW, Abbott LC (1981) Comparative evaluation of quantitative glomerular filtration rate measured by isotopic and nonisotopic methods. Clin Nucl Med 6:150–153

    Article  PubMed  CAS  Google Scholar 

  13. Brochner-Mortensen J, Haahr J, Christoffersen J (1974) A simple method for accurate assessment of the glomerular filtration rate in children. Scand J Clin Lab Invest 33:140–143

    PubMed  CAS  Google Scholar 

  14. Blaufox MD, Aurell M, Bubeck B, Fommei E, Piepsz A, Russell C, Taylor A, Thomsen HS, Volterrani D (1996) Report of the Radionuclides in Nephrourology Committee on renal clearance. J Nucl Med 37:1883–1890

    PubMed  CAS  Google Scholar 

  15. Barbour GL, Crumb CK, Boyd CM, Reeves RD, Rastogi SP, Patterson RM (1976) Comparison of inulin, iothalamate, and 99mTc-DTPA for measurement of glomerular filtration rate. J Nucl Med 17:317–320

    PubMed  CAS  Google Scholar 

  16. Hoek FJ, Kemperman FA, Krediet RT (2003) A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant 18:2024–2031

    Article  PubMed  CAS  Google Scholar 

  17. Larsson A, Malm J, Grubb A, Hansson LO (2004) Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L. Scand J Clin Lab Invest 64:25–30

    Article  PubMed  CAS  Google Scholar 

  18. Le Bricon T, Thervet E, Froissart M, Benlakehal M, Bousquet B, Legendre C, Erlich D (2000) Plasma cystatin C is superior to 24-h creatinine clearance and plasma creatinine for estimation of glomerular filtration rate 3 months after kidney transplantation. Clin Chem 46:1206–1207

    PubMed  Google Scholar 

  19. Rule AD, Bergstralh EJ, Slezak JM, Bergert J, Larson TS (2006) Glomerular filtration rate estimated by cystatin C among different clinical presentations. Kidney Int 69:399–405

    Article  PubMed  CAS  Google Scholar 

  20. Bouvet Y, Bouissou F, Coulais Y, Seronie-Vivien S, Tafani M, Decramer S, Chatelut E (2006) GFR is better estimated by considering both serum cystatin C and creatinine levels. Pediatr Nephrol 21:1299–1306

    Article  PubMed  Google Scholar 

  21. Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310

    Article  PubMed  CAS  Google Scholar 

  22. Perrone RD, Madias NE, Levey AS (1992) Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem 38:1933–1953

    PubMed  CAS  Google Scholar 

  23. Samyn M, Cheeseman P, Bevis L, Taylor R, Samaroo B, Buxton-Thomas M, Heaton N, Rela M, Mieli-Vergani G, Dhawan A (2005) Cystatin C, an easy and reliable marker for assessment of renal dysfunction in children with liver disease and after liver transplantation. Liver Transpl 11:344–349

    Article  PubMed  Google Scholar 

  24. Berding G, Geisler S, Melter M, Marquardt P, Luhr A, Scheller F, Knoop BO, Pfister ED, Pape L, Bischoff L, Knapp WH, Ehrich JH (2010) Estimation of glomerular filtration rate in liver-transplanted children: comparison of simplified procedures using 51Cr-EDTA and endogenous markers with Sapirstein’s method as a reference standard. Pediatr Transplant 14:786–795

    Article  PubMed  Google Scholar 

  25. Blufpand HN, Tromp J, Abbink FC, Stoffel-Wagner B, Bouman AA, Schouten-van Meeteren AY, van Wijk JA, Kaspers GJ, Bokenkamp A (2011) Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy. Pediatr Blood Cancer 57:262–267

    Article  PubMed  Google Scholar 

  26. Bacchetta J, Cochat P, Rognant N, Ranchin B, Hadj-Aissa A, Dubourg L (2011) Which creatinine and cystatin C equations can be reliably used in children? Clin J Am Soc Nephrol 6:552–560

    Article  PubMed  CAS  Google Scholar 

  27. Mention K, Lahoche-Manucci A, Bonnevalle M, Pruvot FR, Declerck N, Foulard M, Gottrand F (2005) Renal function outcome in pediatric liver transplant recipients. Pediatr Transplant 9:201–207

    Article  PubMed  CAS  Google Scholar 

  28. Borrows R, Cockwell P (2007) Measuring renal function in solid organ transplant recipients. Transplantation 83:529–531

    Article  PubMed  Google Scholar 

  29. Takeuchi M, Fukuda Y, Nakano I, Katano Y, Hayakawa T (2001) Elevation of serum cystatin C concentrations in patients with chronic liver disease. Eur J Gastroenterol Hepatol 13:951–955

    Article  PubMed  CAS  Google Scholar 

  30. Demirtas S, Akan O, Can M, Elmali E, Akan H (2006) Cystatin C can be affected by nonrenal factors: a preliminary study on leukemia. Clin Biochem 39:115–118

    Article  PubMed  CAS  Google Scholar 

  31. Chu SC, Wang CP, Chang YH, Hsieh YS, Yang SF, Su JM, Yang CC, Chiou HL (2004) Increased cystatin C serum concentrations in patients with hepatic diseases of various severities. Clin Chim Acta 341:133–138

    Article  PubMed  CAS  Google Scholar 

  32. Boudville N, Salama M, Jeffrey GP, Ferrari P (2009) The inaccuracy of cystatin C and creatinine-based equations in predicting GFR in orthotopic liver transplant recipients. Nephrol Dial Transplant 24:2926–2930

    Article  PubMed  CAS  Google Scholar 

  33. Chew JS, Saleem M, Florkowski CM, George PM (2009) Estimating renal function in oncology patients using cystatin C-based equations. Clin Oncol (R Coll Radiol) 21:425–426

    Article  CAS  Google Scholar 

  34. Gerhardt T, Poge U, Stoffel-Wagner B, Ahrendt M, Wolff M, Spengler U, Palmedo H, Sauerbruch T, Woitas RP (2006) Estimation of glomerular filtration rates after orthotopic liver transplantation: evaluation of cystatin C-based equations. Liver Transpl 12:1667–1672

    Article  PubMed  Google Scholar 

  35. Stake G, Monn E, Rootwelt K, Monclair T (1991) The clearance of iohexol as a measure of the glomerular filtration rate in children with chronic renal failure. Scand J Clin Lab Invest 51:729–734

    Article  PubMed  CAS  Google Scholar 

  36. Houlihan C, Jenkins M, Osicka T, Scott A, Parkin D, Jerums G (1999) A comparison of the plasma disappearance of iohexol and 99mTc-DTPA for the measurement of glomerular filtration rate (GFR) in diabetes. Aust N Z J Med 29:693–700

    Article  PubMed  CAS  Google Scholar 

  37. Schwartz GJ, Furth S, Cole SR, Warady B, Munoz A (2006) Glomerular filtration rate via plasma iohexol disappearance: pilot study for chronic kidney disease in children. Kidney Int 69:2070–2077

    Article  PubMed  CAS  Google Scholar 

  38. Ling Q, Xu X, Li J, Wu J, Chen J, Xie H, Zheng S (2008) A new serum cystatin C-based equation for assessing glomerular filtration rate in liver transplantation. Clin Chem Lab Med 46:405–410

    Article  PubMed  CAS  Google Scholar 

  39. Risch L, Herklotz R, Blumberg A, Huber AR (2001) Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem 47:2055–2059

    PubMed  CAS  Google Scholar 

  40. Qutb A, Syed G, Tamim HM, Al Jondeby M, Jaradat M, Tamimi W, Al Ghamdi G, Al Qurashi S, Flaiw A, Hejaili F, Al Sayyari AA (2009) Cystatin C-based formula is superior to MDRD, Cockcroft–Gault and Nankivell formulae in estimating the glomerular filtration rate in renal allografts. Exp Clin Transpl 7:197–202

    Google Scholar 

  41. White C, Akbari A, Hussain N, Dinh L, Filler G, Lepage N, Knoll GA (2007) Chronic kidney disease stage in renal transplantation classification using cystatin C and creatinine-based equations. Nephrol Dial Transplant 22:3013–3020

    Article  PubMed  CAS  Google Scholar 

  42. White C, Akbari A, Hussain N, Dinh L, Filler G, Lepage N, Knoll GA (2005) Estimating glomerular filtration rate in kidney transplantation: a comparison between serum creatinine and cystatin C-based methods. J Am Soc Nephrol 16:3763–3770

    Article  PubMed  CAS  Google Scholar 

  43. Maillard N, Mariat C, Bonneau C, Mehdi M, Thibaudin L, Laporte S, Alamartine E, Chamson A, Berthoux F (2008) Cystatin C-based equations in renal transplantation: moving toward a better glomerular filtration rate prediction? Transplantation 85:1855–1858

    Article  PubMed  CAS  Google Scholar 

  44. Zahran A, Qureshi M, Shoker A (2007) Comparison between creatinine and cystatin C-based GFR equations in renal transplantation. Nephrol Dial Transplant 22:2659–2668

    Article  PubMed  CAS  Google Scholar 

  45. Poge U, Gerhardt T, Stoffel-Wagner B, Palmedo H, Klehr HU, Sauerbruch T, Woitas RP (2006) Cystatin C-based calculation of glomerular filtration rate in kidney transplant recipients. Kidney Int 70:204–210

    Article  PubMed  CAS  Google Scholar 

  46. Poge U, Gerhardt T, Woitas RP (2008) Equations to estimate GFR using serum cystatin C in kidney transplant recipients. Am J Kidney Dis 52:383–384

    Article  PubMed  Google Scholar 

  47. Huang SH, Macnab JJ, Sontrop JM, Filler G, Gallo K, Lindsay RM, Clark WF (2011) Performance of the creatinine-based and the cystatin C-based glomerular filtration rate (GFR) estimating equations in a heterogenous sample of patients referred for nuclear GFR testing. Transl Res 157:357–367

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of Interest statement

There are no conflicts of interest to disclose.

Financial statement

No financial support was received.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John J. Bissler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nehus, E.J., Laskin, B.L., Kathman, T.I. et al. Performance of cystatin C-based equations in a pediatric cohort at high risk of kidney injury. Pediatr Nephrol 28, 453–461 (2013). https://doi.org/10.1007/s00467-012-2341-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-012-2341-3

Keywords

Navigation